Induced pluripotent stem cells (IPS cells) promise to revolutionize the study of muscle disease. iPS cells, made by introducing transcription factors into primary cell cultures, resemble embryonic stem cells, and can be used to study developmental mechanisms, their alteration in disease states, and to investigate the effects of drugs to correct the defect. Our scientific goal in this proposal is to develop methods for rapid creation of non-genetically modified iPS cells from selected patients with identified muscle disease. Success with these methods will improve efficiency and effectiveness of generation of iPS cells from specific disease fibroblasts maintained in Clinical Repository Research Core. These will be used to study the developmental pathology of these muscle diseases and to lay the basis for future cell therapy applications. An element of phenotypic characterization of the cells during differentiation will use the Force Assessment Research Core to determine whether identified muscle disease mutations alter force generation compared to wild type cells treated similarly. Specific Aims of the proposal are: Specific aim 1: To prepare iPS cells using a non-integrating viral vector. The working hypothesis is that integration into the genome is not required to bring about reprogramming to the iPS phenotype. Specific aim 2: To substitute less hazardous components in the preparation of iPS cells. The working hypothesis is that chromatin opening, rather than oncogenic transformation, is required to enable reprogramming to the iPS phenotype.